Fly consortium uncovers swarm of novel findings

An international research consortium of scientists today announced publications comparing the genome sequences of 12 closely related fruit fly species, 10 of which were sequenced for the first time.

Supported by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), the analyses describe how evolution has shaped the genomes of these important model organisms for genetic research and identify thousands of novel genes and other functional elements in insect genomes.

The lowly fruit fly is one of the most important model organisms in genetic research. In studies dating back nearly a century, researchers used fruit flies to discover the basic rules of inheritance and to study how a single cell, the fertilized egg, develops into a whole animal. Because fruit flies are easy to work with in laboratory settings, they continue to be used as a model to study fundamental biological processes that occur in many living things, including humans.

Although fruit flies have a genome that is 25 times smaller than the human genome, many of the flies' genes correspond to those in humans and control the same biological functions. In recent years, fruit fly research has led to discoveries related to the influence of genes on diseases, animal development, population genetics, cell biology, neurobiology, behaviour, physiology and evolution.

In a paper published this week in the journal Nature, the Drosophila 12 Genomes Consortium presents the genome sequences and preliminary analysis of the genomes of 10 species â€” D. sechellia, D. simulans, D. yakuba, D. erecta, D. ananassae, D. persimilis, D. willistoni, D. mojavensis, D. virilis and D. grimshawi â€” and compare these new genome sequences with that of Drosophila melanogaster, which was published in 2000, and D. pseudoobscura, published in 2005.

The work was carried out by hundreds of scientists from more than 100 institutions in 16 countries. The sequencing of the ten new genomes was led by Agincourt Bioscience Corp, Beverly, Massachusetts, a former member of NHGRI's Large-Scale Sequencing Research Network.

Ten institutes in the UK, including The University of Manchester, University of Edinburgh, University of Oxford, University of Cambridge, the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, contributed to the effort.

Co-author Dr Casey Bergman, from The University of Manchester, said: "One of the great opportunities of now having multiple closely related Drosophila genomes is to finally uncover the mechanisms of genome evolution that lead to the diversity of animal form and behaviour.

"Previous efforts that sequenced distantly related genomes allowed us glimpses into the product of evolution, but the evolutionary time between them was too vast to learn much about the evolutionary process."

To the average person, one fruit fly hovering around an overripe banana looks pretty much like any other. Researchers found that, at first glance, the genomes of the various types of fruit flies appear quite similar. But a more detailed examination reveals that only 77 per cent of the approximately 13,700 protein-coding genes in D. melanogaster are shared with all of the other 11 species.

Scientists observed that different regions of the fruit fly genomes, including protein-coding genes and gene families, are evolving at different rates. For example, genes involved in taste and smell, detoxification and metabolism, sex and reproduction, and immunity and defence appear to be the most rapidly evolving in the fruit fly genomes.

The findings suggest that these particular protein-coding genes likely evolve in the fruit fly genome as a result of adaptation to changing environments and sexual selection. For instance, the fruit fly species D. sechellia, whose population lives on the Seychelles islands in the Indian Ocean, is losing gustatory (taste) receptors approximately five times faster than other fruit fly species that generally encounter a more diverse set of foods than those available on an island.

"Our analyses only represent a small portion of questions that can be answered in the context of these 12 species," said co-author Dr Andrew Clark, from Cornell University, Ithaca, New York.

"Today's findings represent an important starting point for future research aimed at understanding the function of the genome features we discovered and their relevance to the human genome."

In a surprising finding, researchers found that the genes that produce selenoproteins appear to be absent in the D. willistoni genome. Selenoproteins are responsible for reducing excess amounts of the mineral selenium, an antioxidant found in a variety of food sources. Selenoproteins are present in all animals, including humans. D. willistoni appears to be the first animal known to lack these proteins. However, researchers suggest that D. willistoni may possibly encode selenoproteins in a different way, opening a new avenue for further research.

Commenting on the consortium's work, Dr Francis Collins, director of NHGRI, said: "This remarkable scientific achievement underscores the value of sequencing and comparing many closely related species, especially those with great potential to enhance our understanding of fundamental biological processes.

"Thanks to the consortium's hard work, scientists around the world now have a rich new source of genomic data that can be mined in many different ways and applied to other important model systems as well as humans."

For example, a paper in Nature led by Stark et al. used the 12 fruit fly genomes to identify thousands of new genes and other functional elements. This work will bolster efforts to find all functional elements in the reference genome sequence of D. melanogaster.

Specifically, Stark et al. discovered 1,193 new protein-coding sequences and called into question 414 sequences previously reported as protein-coding genes in the D. melanogaster genome sequence. In addition, they found hundreds of novel functional elements across the 12 fruit fly genomes, including: non-protein coding genes; regulatory elements involved in the control of gene transcription; and DNA sequences that mediate the structure and dynamics of chromosomes.

The fruit fly genome sequences and details about the information encoded by these genomes are publicly available from the NHGRI-funded FlyBaseproject (a collaboration of groups at Harvard,University, Indiana University and the University of Cambridge), (http://flybase.bio.indiana.edu) and from NIH's National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov), the European Molecular Biology laboratory's Nucleotide Sequence Database, EMBL-Bank (http://www.ebi.ac.uk/embl/index.html), and the DNA Data Bank of Japan, DDBJ (www.ddbj.nig.ac.jp). Living stocks of the 12 sequenced species are available to the research community through the NSF- supported Tucson Drosophila Species Stock Center at the University of Arizona (http://stockcenter.arl.arizona.edu/).